CD133, also known as Prominin-1 is a pentaspan, highly glycosylated, membrane glycoprotein that is associated with cholesterol in the plasma membrane. Though this protein is known to define a broad population of cells, including somatic stem and progenitor cells, and is expressed in various developing epithelial and differentiated cells, its exact function is still being elucidated. It has however been linked to the Notch-signalling pathway which is critical for binary cell fate, differentiation of intestinal epithelium, and lymphopoiesis (Ulasov et al. 2011. Mol Med 17:103-12). More interest has been shown in this molecule in recent years due to it being thought to be a marker of cancer stem cells (CSCs) in a number of cancers. Indeed, growing evidence has shown that CD133 is expressed on CSCs in a number of cancers, and there is an enhanced tumorigenic potential of CD133+ cells versus their negative counterparts in immunodeficient mice (Dittfeld et al. 2009. Radiother Oncol 92:353-61).
Immunotherapy has had a great impact on the treatment of cancer in recent years. However, the use of antibodies, even humanised antibodies, can lead to adverse side effects that can be fatal (Hansel et al. 2010. Nat Rev Drug Discov 9:325-38). This has led to the search for ‘bigger and better’ options. There have been several attempts made to use nucleic acids as therapeutics though these have met with disappointing results, not least because of the failure of these nucleic acids to enter the cell (Shigdar et al. 2011. Br J Haematol 155:3-13).
Chemical antibodies, termed aptamers, have been increasingly utilised for clinical applications in the last twenty years. Indeed, one aptamer, pegaptanib (an anti-VEGF aptamer) has been approved by the FDA and several more are in clinical trials. Increased interest in the use of aptamers for therapy is due to several reasons, including the fact that they exhibit no immunogenicity, little batch-to-batch variation due to being chemically synthesized, and are more stable than conventional antibodies. Due to their small size, they also show superior tumour penetration. However, their most important feature is the ability to attach these aptamers to nanoparticles, drugs, imaging agents or other nucleic acid therapeutics without loss-of-function (Meng et al. 2012. PLoS One 7:e33434). This functionalisation is leading to new and more targeted therapies, with fewer side effects than current treatment modalities (Meng et al. 2012 supra). When compared to conventional treatment which is largely a passive process, targeted delivery systems are much more effective. For an aptamer to be an effective drug delivery agent, the aptamer must bind to its target on the cell surface and be internalised within a short period of time.